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https://www.hematology.org/Advocacy/Policy-News/2011/938.aspx

Presidential Message on National Sickle Cell Disease Awareness Month

https://www.whitehouse.gov/briefings-statements/presidential-message-national-sickle-cell-disease-awareness-month-2/

National Sickle Cell Disease Awareness Month is a time to acknowledge the challenges faced by Americans with sickle cell disease (SCD) and to reaffirm our commitment to increasing the quality, affordability, and accessibility of different treatment options.

SCD is an inherited red blood cell disorder that is most prevalent among those who have ancestors from sub-Saharan Africa and certain regions of South and Central America.  In the United States, SCD occurs in 1 out of every 365 African-American births and 1 out of every 16,300 Hispanic-American births.  Beginning in early childhood, people with SCD experience a lifetime of crippling pain, challenging disabilities, and often premature death.  The Centers for Disease Control and Prevention estimates medical expenses of children with SCD average between $11,000 and $14,000, with nearly 40 percent of these patients requiring at least one hospital stay.

While American research and innovation have led to medical advances that provide a wide array of treatments for improving the prognosis of children living with SCD, many can be used only for a specific subset of patients.  Far too many patients who could benefit from treatments such as stem cell or bone marrow transplants are not identified until they have already experienced a debilitating medical episode that causes irreversible organ damage.  The National Institutes of Health is working to address this through research to identify children who are more likely to suffer from severe SCD through genetic modifiers.  We want to know which children are at risk and treat them before they experience permanent organ deterioration.  My Administration is also exploring new payment models to make these treatments and potential cures more affordable.  We are also excited to be working with several organizations in developing education and training programs that equip healthcare providers with skills and training to better identify and treat this disease.

We will always stand strong with those battling this condition and remain committed to improving the quality of life of those living with SCD.

Obstacles to use of patient expertise to improve care: a co-produced longitudinal study of the experiences of young people with sickle cell disease in non-specialist hospital settings

Involving young people in their own healthcare is a global priority, yet we know little about how this might work in practice. In this paper, co-produced between academic researchers and people with lived experiences of sickle cell and its treatment, we examine how young people with sickle cell disease attempt to use their expertise in their own condition during emergency hospital admissions and through encounters with healthcare workers who are not sickle cell specialists. Our qualitative longitudinal research in England examined young people’s experiences of hospital encounters via repeat and one-off interviews. We show that young people’s expertise is sometimes undermined, including not being taken seriously when they report pain. They face barriers to care in non-specialist wards, particularly when they are alone with nobody to advocate for them. Although healthcare services use rhetoric that encourages young people to take control of their health and act as patient experts, in practice young people’s expertise is routinely ignored. To improve health service quality, and meet the needs of young people, young people’s own expertise must be better supported in routine interactions with healthcare providers.

https://www.tandfonline.com/doi/full/10.1080/09581596.2019.1650893

Film festival examines minority health topics

This past weekend, Milwaukee hosted a film festival that was the first of its kind not only in the city, but in the United States.

The Minority Health Film Festival, which ran Sept. 12-15, was the country’s first film festival created to address the topic, said Heidi Moore, director of emerging markets and inclusion at Froedtert & The Medical College of Wisconsin and one of the festival’s organizers.

A featured film driven by personal experience is Jaqai Mickelson’s “Spilled Milk.” The documentary addresses the issue of sickle cell disease. The disease, Clayton-Jones said, is a genetic abnormality that causes blood cells to be sickle shaped. It causes complications of “traffic jams of cells” which can result in pain and severe health risks.

Mickelson documents his best friend Omar’s experience living with the disease in an effort to spread awareness of the affliction which in the United States primarily affects African American populations.

While sickle cell disease is still one of the most common inherited genetic diseases, Clayton-Jones said, and is not widely known among health professionals in the United States.

It was Clayton-Jones’s idea to bring the film to Milwaukee. As president of the International Association of Sickle Cell Nurses and Professional Associates, Clayton-Jones said she feels passionate about spreading awareness of the disease, which afflicts a population that “suffers from an incredible amount of stigma and social injustice.”

Clayton-Jones suggested airing the documentary to Moore and Monique Graham, the director of community engagement at Froedtert & The Medical College of Wisconsin, unaware that they were already in the process of putting together a film festival focusing on the very topic “Spilled Milk” addresses: health and minority communities. Fittingly, Clayton-Jones said, September is Sickle Cell Awareness Month.

Clayton-Jones participated in the discussion panel after the film, and Marquette officially sponsored the “Spilled Milk” showing.

While the Minority Health Film Festival addressed a variety of health issues involving a variety of communities, many of the films and discussions shared a common theme: hope.

To watch Spilled Milk go to https://www.spilledmilkmovie.com/

New  Book Resource: Living Well with Sickle Cell

Families receiving a SCD diagnosis over the past 4-5 years at UPMC Children’s Hospital were given the earlier version of this resource. We surveyed parents and caregivers and incorporated their feedback into this new publication.  

100% of the proceeds benefit children with sickle cell disease and their families across the lifespan through The Children’s Sickle Cell Foundation.   The goal is to get this resource into the hands of the families through sickle cell clinics and community based programs.

Hilton Publishing Bookstore: https://hiltonpub.com/bookstore/product/living-well-with-sickle-cell-2019/  

Smile.amazon.com https://smile.amazon.com/Living-Well-Sickle-Cell-Handbook/dp/0998328243/ref=pd_ybh_a_1?_encoding=UTF8&psc=1&refRID=1CQMKTCGQTCXR7XFQKP7

Articles in the medical literature

1. Cochrane Database Syst Rev. 2019 Sep 18;9:CD006110. doi: 10.1002/14651858.CD006110.pub5. [Epub ahead of print]Antibiotics for treating acute chest syndrome in people with sickle cell disease.Martí-Carvajal AJ1Conterno LOKnight-Madden JM..AbstractBACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. This is an update of a Cochrane Review first published in 2007, and most recently updated in 2015.OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination):1. is effective for acute chest syndrome compared to placebo or standard treatment;2. is safe for acute chest syndrome compared to placebo or standard treatment; Further objectives are to determine whether there are important variations in efficacy and safety:3. for different treatment regimens,4. by participant age, or geographical location of the clinical trials.SEARCH METHODS: We searched The Group’s Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 23 October 2017), African Index Medicus (1982 to 23 October 2017) and trial registries (23 October 2017).Date of most recent search of the Haemoglobinopathies Trials Register: 10 July 2019.SELECTION CRITERIA: We searched for published or unpublished randomized controlled trials.DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane methodologies, but no eligible randomized controlled trials were identified.MAIN RESULTS: For this update, we were unable to find any randomized controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease.AUTHORS’ CONCLUSIONS: This update was unable to identify randomized controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. While randomized controlled trials are needed to establish the optimum antibiotic treatment for this condition, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated.
PMID: 31531967 
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2. Pediatrics. 2019 Sep 17. pii: e20184105. doi: 10.1542/peds.2018-4105. [Epub ahead of print]Newborn Screening for Sickle Cell Disease Using Point-of-Care Testing in Low-Income Setting.Alvarez OA1,2Hustace T3,2Voltaire M2Mantero A4Liberus U2Saint Fleur R2..AbstractBACKGROUND: Newborn screening provides early diagnosis for children with sickle cell disease (SCD), reducing disease-related mortality. We hypothesized that rapid point-of-care (POC) Sickle SCAN would be reliable in Haiti and would assist newborn screening.METHODS: Dried blood specimens were obtained from infant heel sticks and analyzed by isoelectric focusing (IEF) at a public hospital in Cap-Haïtien during a 1-year period. A total of 360 Guthrie cards were also analyzed for quality assurance by high-performance liquid chromatography at the Florida Newborn Screening Laboratory. In addition, two-thirds of the infants were also screened by the POC to assess differences with the IEF. The hemoglobinopathy incidence and the specificity and sensitivity of the POC scan were assessed.RESULTS: Overall, 1.48% of the children screened positive for SCD. The specificity and the sensitivity of POC Sickle SCAN were 0.97 (confidence interval 0.95-0.99) and 0.90 (confidence interval 0.55-1.00), respectively, relative to high-performance liquid chromatography gold standard. The confirmatory testing rate was 75% before POC and improved to 87% after POC was added for dual screening. Confirmatory testing revealed that 0.83% of children screened had SCD. Children who screened positive for SCD by POC started penicillin earlier, had their first pediatric follow-up a median of 38 days earlier, and received antipneumococcal vaccination on time when compared with those who screened positive for SCD by IEF alone.CONCLUSIONS: The observational study revealed a high incidence of SCD among Haitian newborns. Sickle SCAN had excellent specificity and sensitivity to detect SCD during newborn screening and shortened health care access for children positive for SCD.Copyright © 2019 by the American Academy of Pediatrics.
PMID: 31530717 
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Conflict of interest statementPOTENTIAL CONFLICT OF INTEREST: Dr Alvarez has been an advisory board member for Novartis related to drugs tested or used in patients with sickle cell disease; the other authors have indicated they have no potential conflicts of interest to disclose.
3. JMIR Pediatr Parent. 2018 Sep 25;1(2):e11058. doi: 10.2196/11058.Exploring the Needs of Adolescents With Sickle Cell Disease to Inform a Digital Self-Management and Transitional Care Program: Qualitative Study.Kulandaivelu Y1,2Lalloo C1,2Ward R3Zempsky WT4Kirby-Allen M5Breakey VR6,7Odame I5,8Campbell F9,10Amaria K11Simpson EA12,13Nguyen C1George T1AbstractBACKGROUND: Accessible self-management interventions are critical for adolescents with sickle cell disease to better cope with their disease, improve health outcomes and health-related quality of life, and promote successful transition to adult health care services. However, very few comprehensive self-management and transitional care programs have been developed and tested in this population. Internet and mobile phone technologies can improve accessibility and acceptability of interventions to promote disease self-management in adolescents with sickle cell disease.OBJECTIVE: The aim of this study was to qualitatively explore the following from the perspectives of adolescents, parents, and their health care providers: (1) the impact of sickle cell disease on adolescents to identify challenges to their self-management and transitional care and (2) determine the essential components of a digital self-management and transitional care program as the first phase to inform its development.METHODS: A qualitative descriptive design utilizing audio-recorded, semistructured interviews was used. Adolescents (n=19, aged 12-19 years) and parents (n=2) participated in individual interviews, and health care providers (n=17) participated in focus group discussions and were recruited from an urban tertiary care pediatric hospital. Audio-recorded data were transcribed verbatim and organized into categories inductively, reflecting emerging themes using simple content analysis.RESULTS: Data were categorized into 4 major themes: (1) impact of sickle cell disease, (2) experiences and challenges of self-management, (3) recommendations for self-management and transitional care, and (4) perceptions about a digital self-management program. Themes included subcategories and the perspectives of adolescents, parents, and health care providers. Adolescents discussed more issues related to self-management, whereas health care providers and parents discussed issues related to transition to adult health services.CONCLUSIONS: Adolescents, parents, and health care providers described the continued challenges youth with sickle cell disease face in terms of psychosocial impacts and stigmatization. Participants perceived a benefit to alleviating some of these challenges through a digital self-management tool. They recommended that an effective digital self-management program should provide appropriate sickle cell disease-related education; guidance on developing self-advocacy and communication skills; empower adolescents with information for planning for their future; provide options for social support; and be designed to be engaging for both adolescents and parents to use. A digital platform to deliver these elements is an accessible and acceptable way to address the self-management and transitional care needs of adolescents.©Yalinie Kulandaivelu, Chitra Lalloo, Richard Ward, William T Zempsky, Melanie Kirby-Allen, Vicky R Breakey, Isaac Odame, Fiona Campbell, Khush Amaria, Ewurabena A Simpson, Cynthia Nguyen, Tessy George, Jennifer N Stinson. Originally published in JMIR Pediatrics and Parenting (http://pediatrics.jmir.org), 25.09.2018.PMCID: PMC6716437 Free PMC Article
PMID: 31518307 
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5. Am J Physiol Cell Physiol. 2019 Sep 11. doi: 10.1152/ajpcell.00287.2019. [Epub ahead of print]Hemoglobin Alters Vitamin Carrier Uptake and Vitamin D Metabolism in Proximal Tubule Cells: Implications for Sickle Cell Disease.Gliozzi ML1Rbaibi Y1Long KR1Vitturi DA2Weisz OA3.Author information: 
1. Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States.
2. Department of Pharmacology and Chemical Biology, Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States.
3. Renal-Electrolyte Division, Department of Medicine, Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States.AbstractKidney disease, including proximal tubule (PT) dysfunction, and vitamin D deficiency are among the most prevalent complications in sickle cell disease (SCD) patients. Although these two comorbidities have never been linked in SCD, the PT is the primary site for activation of vitamin D. Precursor 25(OH)D bound to vitamin D binding protein (DBP) is taken up by PT cells via megalin/cubilin receptors, hydroxylated to the active 1,25(OH)2D form, and released into the bloodstream. We tested the hypothesis that cell-free hemoglobin (Hb) filtered into the PT lumen impairs vitamin D uptake and metabolism. Hb at concentrations expected to be chronically present in the ultrafiltrate of SCD patients competed directly with DBP for apical uptake by PT cells. By contrast, uptake of retinol binding protein was impaired only at considerably higher Hb concentrations. Prolonged exposure to Hb led to increased oxidative stress in PT cells and to a selective increase in mRNA levels of the CYP27B1 hydroxylase, although protein levels were unchanged. Hb exposure also impaired vitamin D metabolism in PT cells, resulting in reduced ratio of 1,25(OH)2D:25(OH)D. Moreover, plasma levels of 1,25(OH)2D were reduced in a mouse model of SCD. Together, our data suggest that Hb released by chronic hemolysis has multiple effects on PT function that contribute to vitamin D deficiency in SCD patients.
PMID: 31509446 
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6. Br J Haematol. 2019 Sep 11. doi: 10.1111/bjh.16188. [Epub ahead of print]Antenatal screening for haemoglobinopathies: current status, barriers and ethics.Chakravorty S1Dick MC1.AbstractSickle cell disease (SCD) and thalassaemia are genetic disorders that are caused by errors in the genes for haemoglobin and are some of the most common significant genetic disorders in the world, resulting in significant morbidity and mortality. Great disparities exist in the outcome of these conditions between resource- rich and resource-poor nations. Antenatal screening for these disorders aims to provide couples with information about their reproductive risk and enable them to make informed reproductive choices; ultimately reducing the likelihood of children being born with these conditions. This review provides an overview of the current status of antenatal, pre-marital and population screening of SCD and thalassaemia in countries with both high-and low prevalence of these conditions, methods of screening in use, and discusses some of the pitfalls, ethical issues and controversies surrounding antenatal screening. It also discusses outcomes of some screening programmes and recognises the need for the establishment of antenatal screening in areas where their prevalence is highest; namely sub-Saharan Africa and India.© 2019 British Society for Haematology and John Wiley & Sons Ltd.
PMID: 31509241 
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7. J Blood Med. 2019 Aug 30;10:307-311. doi: 10.2147/JBM.S191423. eCollection 2019.Profile of crizanlizumab and its potential in the prevention of pain crises in sickle cell disease: evidence to date.Riley TR1Riley TT1..AbstractSickle cell disease (SCD) is one of the most common inherited blood disorders globally. It is a grouping of autosomal recessive genetic disorders identified by a genetic mutation that replaces glutamic acid with valine at the sixth amino acid on the hemoglobin β-globin chain. Millions of people around the world live with a severe genotype of SCD that is often associated with occlusion of the microvasculature resulting in episodes of severe pain and multiple organ system dysfunction. These episodes, commonly categorized as vaso-occlusive crises (VOC), are a distinctive clinical presentation of SCD which represents the majority of SCD morbidity and associated hospitalizations. Though the complete process by which these crises occur is complex and not fully outlined, evidence reveals this process to be multifactorial and heterocellular. For nearly two decades, hydroxyurea was the only FDA-approved therapy for SCD. Evidence to date shows that hydroxyurea treatment significantly reduces the rate of VOC, hospitalizations, and mortality. Despite these benefits, adherence remains problematic due to a variety of adverse effects and interpatient variability connected with hydroxyurea therapy. Crizanlizumab, an adhesion inhibitor of sickled red blood cells, was recently granted breakthrough therapy designation. Results of a phase 2 study have reported a successful reduction in annual rates of vaso-occlusive crisis with a favorable safety profile. This paper reviews the available literature concerning crizanlizumab use in patients with SCD.PMCID: PMC6720158 Free PMC Article
PMID: 31507334 
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Conflict of interest statementThe authors report no conflicts of interest in this work.
8. Pharmacotherapy. 2019 Sep 10. doi: 10.1002/phar.2329. [Epub ahead of print]Systematic review of L-glutamine for prevention of vaso-occlusive pain crisis in patients with sickle cell disease.Hutcherson TC1Cieri-Hutcherson NE2Conway-Habes EE3Burns BN4White NA4..AbstractINTRODUCTION: L-glutamine was approved by the United States Food and Drug Administration (FDA) for sickle cell disease (SCD) in 2017. Vaso-occlusive crisis (VOC) occurs in persons with SCD and is associated with acute pain episodes. This systematic review summarizes the evidence for L-glutamine in the prevention of VOC and associated pain in patients with SCD.METHODS: Medline, Embase, and International Pharmaceutical Abstracts were searched for records reporting on L-glutamine use in persons with SCD. Eligibility criteria identified primary reports of investigations conducted in humans who were administered L-glutamine, reported on outcomes related to VOC or associated pain, published in English, and available as full text. All relevant efficacy, safety, participant demographic data, and study method characteristics were extracted and documented. Risk-of-bias assessments were conducted using the Risk of Bias in Non-Randomized Studies – of Interventions (ROBINS-I) tool and the revised Cochrane risk-of-bias tool for randomized studies.RESULTS: Three studies assessing the effect of exogenous L-glutamine administration in patients with SCD met eligibility criteria, including one prospective, nonrandomized, controlled study and two prospective, randomized, controlled trials. Rate of VOC and related hospitalizations were reduced in patients receiving L-glutamine, although some conflicting results were noted between studies. L-glutamine was generally well tolerated. Limitations of one or more of the eligible studies included small sample size, nonblinding, and study groups that differed at baseline.DISCUSSION: L-glutamine has limited high-quality evidence supporting its use. Although L-glutamine is FDA approved for the prevention of frequent episodes of VOC pain, only one randomized controlled trial has strong evidence to support this indication. Based on the results of a systematic review, L-glutamine may be considered for patients unable to receive hydroxyurea or in addition to hydroxyurea for reduction in VOC and associated pain.© 2019 Pharmacotherapy Publications, Inc.
PMID: 31505045 
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9. Cochrane Database Syst Rev. 2019 Sep 9;9:CD011358. doi: 10.1002/14651858.CD011358.pub3. [Epub ahead of print]Magnesium for treating sickle cell disease.Than NN1Soe HHKPalaniappan SKAbas ABDe Franceschi L.AbstractBACKGROUND: Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life. This is an updated version of the review.OBJECTIVES: To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease.SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register: 03 February 2019.Date of last search of other resources (clinical trials registries): 04 April 2019.SELECTION CRITERIA: We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium.DATA COLLECTION AND ANALYSIS: Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies.MAIN RESULTS: We included five randomized placebo-controlled studies with a total of 386 participants (aged three to 53 years). Of these, two shorter parallel studies (n = 306) compared intravenous magnesium sulphate to placebo (normal saline) for admission to hospital due to a vaso-occlusive crisis, for which we were able to analyse data. The quality of evidence was moderate for studies in this comparison, mainly due to limitations due to risk of bias and imprecision. Two of the three longer-term studies comparing oral magnesium pidolate to placebo had a cross-over design. The third was a parallel factorial study which compared hydroxyurea and oral magnesium to each other and to placebo over a longer period of time; we only present the comparison of oral magnesium to placebo from this study. The quality of evidence was very low with uncertainty of the estimation.The eight-hourly dose levels in the two studies of intravenous magnesium were different; one used 100 mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104) reported the mean daily pain score while hospitalised (a non-significant difference between groups, moderate quality evidence). The second study (n = 202) reported a number of child- and parent-reported quality of life scores. None of the scores showed any difference between treatment groups (low quality evidence). Data from one study (n = 106) showed no difference in length of stay in hospital between groups (low quality evidence). Both studies reported on adverse events, but not defined by severity as we had planned. One study showed significantly more participants receiving intravenous magnesium experienced warmth at infusion site compared to placebo; there were no differences between groups for other adverse events (low quality evidence).Three studies (n = 80) compared oral magnesium pidolate to placebo. None of them reported data which we were able to analyse. One study (n = 24) reported on the number of painful days and stated there was no difference between two groups (low quality evidence). None of the studies reported on quality of life or length of hospital stay. Two studies (n = 68) reported there were no differences in levels of magnesium in either plasma or red blood cells (moderate quality evidence). Two studies (n = 56) reported adverse events. One reported episodes of mild diarrhoea and headache, all of which resolved without stopping treatment. The second study reported adverse events as gastrointestinal disorders, headache or migraine, upper respiratory infections and rash; which were all evenly distributed across treatment groups (moderate quality evidence).AUTHORS’ CONCLUSIONS: Moderate to low quality evidence showed neither intravenous magnesium and oral magnesium therapy has an effect on reducing painful crisis, length of hospital stay and changing quality of life in treating sickle cell disease. Therefore, no definitive conclusions can be made regarding its clinical benefit. Further randomized controlled studies, perhaps multicentre, are necessary to establish whether intravenous and oral magnesium therapies have any effect on improving the health of people with sickle cell disease.
PMID: 31498421 
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10. Am J Med Qual. 2019 Sep 9:1062860619873402. doi: 10.1177/1062860619873402. [Epub ahead of print]Clinical Transformation in Care for Patients With Sickle Cell Disease at an Urban Academic Medical Center.Rizk S1Axelrod D1Riddick-Burden G1Congdon-Martin E1McKenzie S1Haines C1Ward L1McAna J1Crawford AG1.Author information: 
1. Thomas Jefferson University, Philadelphia, PA.AbstractThis article demonstrates effects on utilization of a clinical transformation: changing locus of care from a dedicated sickle cell day unit to an approach that “fast-tracks” patients through the emergency department (ED) into an observation unit with 24/7 access. Retrospective quantitative analyses of claims and Epic electronic medical record data for patients with sickle cell disease treated at Thomas Jefferson University (inpatient and ED) assessed effects of the clinical transformation. Additionally, case studies were conducted to confirm and deepen the quantitative analyses. This study was approved by the Thomas Jefferson University Institutional Review Board. The quantitative analyses show significant decreases in ED and inpatient utilization following the transformation. These effects likely were facilitated by increased observation stays. This study demonstrated the impact on utilization of transformation in care (from dedicated day unit to an approach that fast-tracks patients into an observation unit). Additional case studies support the quantitative findings.
PMID: 31496258 
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11. Curr Opin Hematol. 2019 Sep 3. doi: 10.1097/MOH.0000000000000545. [Epub ahead of print]Allogenic hematopoietic stem cell transplantation in sickle cell disease.Galal A1Asslan M2,3..AbstractPURPOSE OF REVIEW: Discussing the currently available HSCT options for Hb SS patients highlighting advantages and disadvantages of each modality in the light of recently published data.RECENT FINDINGS: When MSD is available, myeloablative regimen is the preferred approach for otherwise healthy children whereas the nonmyeloablative (NMA) regimen is of choice for adults as well as children with SCD-associated morbidities. Mixed chimerism is common especially with NMA conditioning and is usually enough for cure. Alternative donor HSCT outcomes are progressively improving especially with posttransplant cyclophosphamide for GVHD prophylaxis.SUMMARY: Recent studies comparing HSCT and chronic transfusion in Hb SS patients increasingly come in favor of HSCT arm. Advances in HSCT field led to donor pool expansion and better tolerated regimens. It is easier now to tailor a personalized transplantation plan for almost every patient. A successful management plan should be sufficiently comprehensive addressing patients’ and families’ social and psychological concerns to ensure compliance and improve outcome.
PMID: 31490318 
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12. Am J Hematol. 2019 Sep 6. doi: 10.1002/ajh.25635. [Epub ahead of print]Ischemic Stroke in Children and Young Adults with Sickle Cell Disease in the Post-STOP Era.Kwiatkowski JL1Kanter J2Fullerton HJ3Voeks JH4Debenham E4Brown L4Adams RJ4Post-STOP Study Group..AbstractThe Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) trials established routine transcranial Doppler ultrasound (TCD) screening with indefinite chronic red cell transfusions (CRCT) for children with abnormal TCD as standard of care. Implementation failures and limitations to the STOP protocol may contribute to continued ischemic stroke occurrence. In the “Post-STOP” study, we sought to assess the impact of the STOP protocol on the incidence of ischemic stroke in a multicenter cohort of former STOP and/or STOP 2 trial participants. A central team abstracted data for 2,851 (74%) of the 3,835 children who took part in STOP and/or STOP 2. Data included TCD and neuroimaging results, treatment, laboratory data, and detailed clinical information pertaining to the stroke. Two stroke neurologists independently confirmed each stroke using pre-specified imaging and clinical criteria and came to consensus. Among the 2,808 patients stroke-free at the start of Post-STOP with available follow-up, the incidence of first ischemic stroke was 0.24 per 100 patient-years (95% CI, 0.18, 0.31), with a mean (SD) duration of follow-up of 9.1+3.4 (median 10.3, range (0 -15.4) years. Most (63%) strokes occurred in patients in whom the STOP protocol had not been properly implemented, either failure to screen appropriately with TCD (38%) or failure to transfuse adequately patients with abnormal TCD (25%). This study shows that substantial opportunities for ischemic stroke prevention remain by more complete implementation of the STOP Protocol. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
PMID: 31489983 
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13. Blood Adv. 2019 Sep 10;3(17):2586-2597. doi: 10.1182/bloodadvances.2019031633.Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.McMahon TJ1,2,3Shan S4Riccio DA1Batchvarova M4Zhu H1Telen MJ4Zennadi R4.AbstractSickle red blood cells (SSRBCs) are adherent to the endothelium, activate leukocyte adhesion, and are deficient in bioactive nitric oxide (NO) adducts such as S-nitrosothiols (SNOs), with reduced ability to induce vasodilation in response to hypoxia. All these pathophysiologic characteristics promote vascular occlusion, the hallmark of sickle cell disease (SCD). Loading hypoxic SSRBCs in vitro with NO followed by reoxygenation significantly decreased epinephrine-activated SSRBC adhesion to the endothelium, the ability of activated SSRBCs to mediate leukocyte adhesion in vitro,and vessel obstruction in vivo. Because transfusion is frequently used in SCD, we also determined the effects of banked (SNO-depleted) red blood cells (RBCs) on vaso-occlusion in vivo. Fresh or 14-day-old normal RBCs (AARBCs) reduced epinephrine-activated SSRBC adhesion to the vascular endothelium and prevented vaso-occlusion. In contrast, AARBCs stored for 30 days failed to decrease activated SSRBC adhesivity or vaso-occlusion, unless these RBCs were loaded with NO. Furthermore, NO loading of SSRBCs increased S-nitrosohemoglobin and modulated epinephrine’s effect by upregulating phosphorylation of membrane proteins, including pyruvate kinase, E3 ubiquitin ligase, and the cytoskeletal protein 4.1. Thus, abnormal SSRBC NO/SNO content both contributes to the vaso-occlusive pathophysiology of SCD, potentially by affecting at least protein phosphorylation, and is potentially amenable to correction by (S)NO repletion or by RBC transfusion.PMCID: PMC6737414 Free PMC Article
PMID: 31484636 
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14. Curr Opin Hematol. 2019 Sep 2. doi: 10.1097/MOH.0000000000000541. [Epub ahead of print]Hematopoietic stem cell transplantation and cellular therapy in sickle cell disease: where are we now?Tanhehco YC1Bhatia M2AbstractPURPOSE OF REVIEW: Sickle cell disease (SCD) is a common monogenic disorder that is characterized by an A to T substitution in the β-globin gene that leads to the production of hemoglobin S (HbS). Polymerization of HbS leads to significant morbidity including vaso-occlusion, pain, hemolytic anemia, and end organ damage. Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment; however, suitable donors are not always readily available. This study reviews the current status of allo-HCT and autologous cellular therapies for SCD.RECENT FINDINGS: Alternative sources of allogeneic stem cells from unmatched donors such as cord blood and haploidentical donors are gaining traction. Early experience has shown that better conditioning regimens and graft-versus-host disease prophylaxis are needed before these donor sources can gain widespread use. Clinical trials are underway to determine the feasibility and efficacy of autologous transplantation with gene modified hematopoietic stem cells. Gene therapy strategies include HbS gene correction, gene addition, and hemoglobin F induction. Preliminary results are very encouraging.SUMMARY: Matched sibling allo-HCT for patients with SCD results in more than 90% overall survival and more than 80% event-free survival. Because only 25-30% of patients have a matched sibling donor, alternative donor options such as matched unrelated donors, related haploidentical donors and unrelated umbilical cord blood donors are being considered. Clinical trials investigating various strategies for gene therapy followed by autologous transplantation are underway. One major challenge is obtaining sufficient hematopoietic stem cells for gene therapy. Studies are being conducted on the optimal mobilization regimen and collection strategy.
PMID: 31483336 
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15. Curr Opin Hematol. 2019 Sep 2. doi: 10.1097/MOH.0000000000000540. [Epub ahead of print]Mechanisms of alloimmunization in sickle cell disease.Hudson KE1Fasano RM2,3,4Karafin MS5Hendrickson JE6Francis RO1AbstractPURPOSE OF REVIEW: Red blood cell (RBC) transfusion is an important treatment for some complications of sickle cell disease (SCD). On the contrary, transfusion may lead to alloimmunization to RBC antigens, with such alloantibodies putting patients at risk for acute or delayed hemolysis, and increasing the difficulty of finding compatible RBCs. Patients with SCD are more susceptible to developing RBC alloantibodies than other multiply transfused patient populations, for reasons that are not completely understood. In this review, we summarize the available data about risk factors and underlying mechanisms associated with RBC alloimmunization in SCD.RECENT FINDINGS: Although RBC antigen matching between blood donors and transfusion recipients can decrease alloimmunization, complete matching at all loci is not feasible. Patients with SCD show evidence of increased inflammation at baseline and in times of illness. Resultant changes to the innate and adaptive immune systems presumably influence the development of RBC alloantibodies as well as RBC autoantibodies.SUMMARY: The inflammation and immune dysregulation associated with SCD may be therapeutic targets for preventing the formation of antibodies and/or for mitigating the dangers of existing RBC alloantibodies. As long as RBC transfusion therapy remains an important treatment for SCD, the quest to improve its safety profile will continue.
PMID: 31483335 
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16. J Intensive Care Med. 2019 Sep 2:885066619874041. doi: 10.1177/0885066619874041. [Epub ahead of print]Reversal of Severe Multiorgan Failure Associated With Sickle Cell Crisis Using Plasma Exchange: A Case Series.Zaidi GZ1Rosentsveyg JA1Fomani KF2Louie JP2Koenig SJ1.AbstractOBJECTIVE: Red blood cell exchange (RBCE) is the standard of care for patients with sickle cell disease (SCD) who present with severe vaso-occlusive crisis (VOC). However, subsets of these critically ill patients have progressive multiorgan failure (MOF) despite RBCE therapy. The purpose of this case series is to describe the use of plasma exchange (PLEX) for the treatment of SCD-related MOF that is refractory to RBCE.METHODS: A retrospective case review of patients with severe MOF from sickle cell crisis unresponsive to RBCE who underwent PLEX in a 14-bed adult medical intensive care unit (ICU) at a tertiary care university hospital over a 4-year time period. Key laboratory data including complete blood count, indices of hemolysis, and markers of organ failure were recorded before and after both RBCE and PLEX.RESULTS: Our primary objective is to evaluate the effectiveness of PLEX, in addition to RBCE, on organ dysfunction, laboratory indices, and mortality. Of the 7 patients, 6 survived. Of the patients who survived, all remained hemodynamically stable during PLEX sessions and showed both clinical and laboratory evidences of improvement in hemolysis and organ function. Average time from completion of first PLEX treatment to initial laboratory signs of organ failure reversal for patients who survived was 15.6 hours, the average length of stay in the ICU was 5.6 days, and the average total length of stay in the hospital was 14 days.CONCLUSIONS: Plasma exchange, in addition to RBCE, may be a novel synergistic treatment option to decrease risk of mortality in patients with refractory VOC and MOF.
PMID: 31476954 
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17. Ann Hematol. 2019 Sep 2. doi: 10.1007/s00277-019-03783-y. [Epub ahead of print]Genetic modulators of fetal hemoglobin expression and ischemic stroke occurrence in African descendant children with sickle cell anemia.Nicolau M1Vargas S1Silva M1Coelho A1Ferreira E1Mendonça J1Vieira L1,2Kjöllerström P3Maia R3Silva R4Dias A5Ferreira T5Morais A6Soares IM7Lavinha J1,8Faustino P9,10,11.AbstractSickle cell anemia (SCA) is an autosomal recessive monogenic disease with significant clinical variability. Cerebrovascular disease, particularly ischemic stroke, is one of the most severe complications of SCA in children. This study aimed to investigate the influence of genetic variants on the levels of fetal hemoglobin (Hb F) and biochemical parameters related with chronic hemolysis, as well as on ischemic stroke risk, in ninety-one unrelated SCA patients, children of sub-Saharan progenitors. Our results show that a higher Hb F level has an inverse relationship with the occurrence of stroke, since the group of patients who suffered stroke presents a significantly lower mean Hb F level (5.34 ± 4.57% versus 9.36 ± 6.48%; p = 0.024). Furthermore, the co-inheritance of alpha-thalassemia improves the chronic hemolytic pattern, evidenced by a decreased reticulocyte count (8.61 ± 3.58% versus 12.85 ± 4.71%; p < 0.001). In addition, our findings have confirmed the importance of HBG2 and BCL11A loci in the regulation of Hb F expression in sub-Saharan African SCA patients, as rs7482144_A, rs11886868_C, and rs4671393_A alleles are significantly associated with a considerable increase in Hb F levels (p = 0.019, p = 0.026, and p = 0.028, respectively). Concerning KLF1, twelve different variants were identified, two of them novel. Seventy-three patients (80.2%) presented at least one variant in this gene. However, no correlation was observed between the presence of these variants and Hb F level, severity of hemolysis, or stroke occurrence, which is consistent with their in silico-predicted minor functional consequences. Thus, we conclude that the prevalence of functional KLF1 variants in a sub-Saharan African background does not seem to be relevant to SCA clinical modulation.
PMID: 31478061 
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18. Ann Am Thorac Soc. 2019 Sep;16(9):e17-e32. doi: 10.1513/AnnalsATS.201906-433ST.Identifying Clinical and Research Priorities in Sickle Cell Lung Disease. An Official American Thoracic Society Workshop Report.Ruhl APSadreameli SCAllen JLBennett DPCampbell ADCoates TDDiallo DAField JJFiorino EKGladwin MTGlassberg JAGordeuk VRGraham LMGreenough AHoward JKato GJKnight-Madden JKopp BTKoumbourlis ACLanzkron SMLiem RIMachado RFMehari AMorris CROgunlesi FORosen CLSmith-Whitley KTauber DTerry NThein SLVichinsky EWeir NACohen RTKlings ES.AbstractBackground: Pulmonary complications of sickle cell disease (SCD) are diverse and encompass acute and chronic disease. The understanding of the natural history of pulmonary complications of SCD is limited, no specific therapies exist, and these complications are a primary cause of morbidity and mortality.Methods: We gathered a multidisciplinary group of pediatric and adult hematologists, pulmonologists, and emergency medicine physicians with expertise in SCD-related lung disease along with an SCD patient advocate for an American Thoracic Society-sponsored workshop to review the literature and identify key unanswered clinical and research questions. Participants were divided into four subcommittees on the basis of expertise: 1) acute chest syndrome, 2) lower airways disease and pulmonary function, 3) sleep-disordered breathing and hypoxia, and 4) pulmonary vascular complications of SCD. Before the workshop, a comprehensive literature review of each subtopic was conducted. Clinically important questions were developed after literature review and were finalized by group discussion and consensus.Results:Current knowledge is based on small, predominantly observational studies, few multicenter longitudinal studies, and even fewer high-quality interventional trials specifically targeting the pulmonary complications of SCD. Each subcommittee identified the three or four most important unanswered questions in their topic area for researchers to direct the next steps of clinical investigation.Conclusions: Important and clinically relevant questions regarding sickle cell lung disease remain unanswered. High-quality, multicenter, longitudinal studies and randomized clinical trials designed and implemented by teams of multidisciplinary clinician-investigators are needed to improve the care of individuals with SCD.
PMID: 31469310 
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19. Am J Hematol. 2019 Aug 27. doi: 10.1002/ajh.25626. [Epub ahead of print]Perioperative care of children with sickle cell disease: a systematic review and clinical recommendations.Schyrr F1Dolci M2Nydegger M2Canellini G3Andreu-Ullrich H3Joseph JM4Diezi M1Cachat F5Rizzi M1Renella R1.Author information: .AbstractChildren with sickle cell disease (SCD) require specific perioperative care, and clinical practice in this area remains poorly defined. We aimed to a) conduct a systematic, PRISMA-based review of the literature and any available clinical guidelines, practice recommendations, and extract any valuable information for the “best of available-evidence”-based prevention of perioperative adverse events in children with SCD, b) highlight the most urgent priorities in clinical research. As data sources, US National Library of Medicine, Medline, National Guideline Clearinghouse, International Guideline Network, TRIP databases were searched for any content until January 2019. We also included institutional, consortia and expert group guidelines. Included were reports/guidelines in English, French, German, Italian. Excluded were reports on obstetrical and fetal management. We identified 202 reports/guidelines fulfilling the criteria outlined above. A majority focused on visceral, cardiovascular and orthopedic surgery procedures, and only five were multicenter randomized controlled trials and two prospective randomized studies. After grading of quality of evidence, the extracted data was summarized into clinical recommendations for daily practice. Additionally, we designed a risk-grading algorithm to identify contexts likely to be associated with adverse outcomes. In conclusion, we provide a systematic PRISMA-based review of the existing literature and any ancillary practice and delineate a set of clinical recommendations and priorities for research. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
PMID: 31456233 
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20. Neurosci Lett. 2019 Aug 24:134445. doi: 10.1016/j.neulet.2019.134445. [Epub ahead of print]Neuropathic pain in individuals with sickle cell disease.Sharma D1Brandow AM2..AbstractPain is the most frequently occurring complication of sickle cell disease (SCD) and the leading cause of hospitalizations for affected individuals. Acute pain episodes are also an independent predictor of mortality in individuals with SCD. The pathophysiology of pain in SCD is complex and has been attributed to several biologic factors, including oxidative stress, vaso-occlusion, ischemia-reperfusion injury and inflammation. In spite of this complex biology, painful events requiring hospitalization are simplistically referred to as “acute vaso-occlusive pain episodes” by the hematology community, and subgroups of pain in SCD have not been formally classified. Neuropathic pain is an emerging unique SCD pain phenotype that could be a result of these biologic drivers in SCD. Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system and has been estimated to occur in approximately 25-40% of adolescents and adults with SCD. Diagnostic modalities for neuropathic pain, including validated questionnaires incorporating pain descriptors, quantitative sensory testing and functional neuroimaging, have been evaluated in small to medium-sized cross-sectional studies of adolescents and adults with SCD. However, these diagnostic tests are not currently used in the routine care of individuals with SCD. Age, female gender and hydroxyurea use have been reported to be positively associated with neuropathic pain in SCD, although modifiable risk factors for the prevention of neuropathic pain in this population have not been identified. A few early phase studies have begun to investigate neuropathic pain-specific medications in individuals with SCD. However, evidence-based strategies to target neuropathic pain in SCD are lacking, and the existing literature suggests that neuropathic pain-specific medications are highly underutilized in individuals with SCD. We will review the epidemiology, underlying biology and therapeutic interventions for diagnosis and treatment of neuropathic pain in SCD. We will also highlight opportunities to address critical gaps in knowledge that remain for this under-recognized cause of SCD morbidity.Copyright © 2019. Published by Elsevier B.V.
PMID: 31454562 
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Sickle Cell Conferences and Events

Sickle Cell Disease Association of America’s 47th National Conventionwill be held October 9-12, 2019in Baltimore, MD. https://www.sicklecelldisease.org/2019/01/18/47th-annual-national-convention-call-for-abstracts/

Sickle Cell in Focus 2019will be held October 10 – 11, 2019 in Kingston, Jamaica at The Jamaica Pegasus Hotel. More details can be found at https://www.nhlbi.nih.gov/events/2019/sickle-cell-focus-conference-2019

 5th Annual Sickle Cell Symposium:

Sickle Cell Disease: The Next Generation of Patients and Providers

Saturday November 9th, 2019

at the Charlotte Speedway Club in Concord, NC The link for the Symposium Registration: http://www.cvent.com/d/kyqpb5

The Keynote address will be given by Wayne Frederick, MD, MBA, the 17th President of Howard University. Join us for a day of education focused on the new understanding of sickle cell disease pathophysiology and novel therapeutic approaches to management, culminating with a live Q & A with experts in the field. We ‘re excited and look forward to you attending the event. Info Lawrence.Black@atriumhealth.org

Symposium Registrationhttp://www.cvent.com/d/kyqpb5